Oxygen Species Research Articles

In-situ generation of highly dispersed Au nanoparticles on porous ZnO nanoplates via ion exchange from hydrozincite for VOCs gas sensing

The indoor volatile organic compounds (VOCs) have caught much attention because millions of people are suffering from indoor air pollution. To detect VOCs, various gas sensors with fast response, high sensitivity and high stability have been fabricated by nanocomposite technology. In this study, highly dispersed Au nanoparticles are deposited on porous ZnO nanoplates (Au@ZnO) via ion exchange method from hydrozincite [Zn5(CO3)2(OH)6] without the addition of any surfactants. By immersing hydrozincite precursors into 0.1%–5% HAuCl4 solutions and followed by annealing, several Au@ZnO sensors with size-limited Au nanoparticles are fabricated for the detection of nine types of VOCs. Comparing with pure ZnO nanoplates, the as-prepared Au@ZnO sensors show enhanced sensitivity by 2–9 times at 400°C toward all nine types of VOCs. Also, fast response/recovery time and fine repeatability in the gas-sensing tests are attained. More oxygen species and active sites to the adsorbed VOCs molecules are generated by Au@ZnO hybrids, which lead to the improvement of ZnO-based gas sensor limitation.

Glutathione (GSH) Production as Protective Adaptation Against Light Regime Radiation of Symbiodinium Natural Population

Glutathione (GSH), as a wide range of low molecular weight, which found in marine microalgae and event bacteria, are essential to prevent photooxidation and productivity loss from these Radical Oxigen Species (ROS). Symbiodinium, endo-symbiont of corals, were exposed with different UV radiation combined with irradiance treatments to explore biomass specific initial response. Intracellular glutahione was observed as potential adaptive response of Symbiodinium population under environmental specific stress. The result showed that GSH production increased significantly with increasing irradiance and/or UV levels. GSH concentration was fluctuated among populations exposed by different irradiance treatments, but not effected by UV and irradiance exposure. GSH production as a response of UV exposure was higher than irradiance treatments. Both these high correlative fluctuation of intracellular GSH production and the presence of both treatments indicated protective specific adaptation of Symbiodinium under specific environmental stress, respectively. Keywords: zooxanthellae, irradiance, glutathione (GSH), corals, Fungia

Diallyl trisulfide (DATS) suppresses benzene-induced cytopenia by modulating haematopoietic cell apoptosis

Benzene is a well-known occupational and environmental toxicant associated with cytopenia, which is characterized by a disorder in the peripheral blood cell counts. However, no effective preventive strategy has been developed yet to tackle the exposure to benzene in daily life. The aim of this study was to evaluate the protective effects of diallyl trisulfide (DATS) on benzene-induced haematopoietic damage and to reveal its potential mechanisms of action. In our study, male Sprague-Dawley rats were divided into six groups. Rats were administered with benzene (1.3 g/kg BW by gavage) to establish the benzene poisoning model, while the DATS treatment groups were treated with benzene plus DATS (15 mg/kg, 30 mg/kg, 45 mg/kg, respectively, by gavage) for 28 days. Our results demonstrated that the counts of peripheral blood WBC and RBC decreased to 31.0% and 79.2%, respectively, in the benzene poisoning model group compared to the control. However, blood cell counts were restored by DATS treatment (30 mg/kg, 45 mg/kg). The apoptosis rates of peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were increased to 274% and 284%, respectively, following benzene exposure. Furthermore, expression levels of Bcl-2, PI3K and p-Akt were downregulated and those of Bax were upregulated in both cell types. Moreover, the oxidative parameters (oxygen species, malonaldehyde) were significantly increased, while the non-enzymatic GSH/GSSG ratios and the activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase) were decreased. Interestingly, DATS treatment can restore the WBC number by 267.1% and 304.8% while RBC number by 108.6% and 117.7% in 30,45 mg/k DATS treated groups. In summary, we demonstrated that benzene-induced cytopenia was related to the apoptosis of PBMCs and BMCs, and DATS treatment could prevent benzene-induced cytopenia by suppressing oxidative stress-mediated cell apoptosis via the PI3K/Akt pathway.

Enhanced Carbon Dioxide Electroreduction to Carbon Monoxide over Defect‐Rich Plasma‐Activated Silver Catalysts

AbstractEfficient, stable catalysts with high selectivity for a single product are essential if electroreduction of CO2 is to become a viable route to the synthesis of industrial feedstocks and fuels. A plasma oxidation pre‐treatment of silver foil enhances the number of low‐coordinated catalytically active sites, which dramatically lowers the overpotential and increases the activity of CO2 electroreduction to CO. At −0.6 V versus RHE more than 90 % Faradaic efficiency towards CO was achieved on a pre‐oxidized silver foil. While transmission electron microscopy (TEM) and operando X‐ray absorption spectroscopy showed that oxygen species can survive in the bulk of the catalyst during the reaction, quasi in situ X‐ray photoelectron spectroscopy showed that the surface is metallic under reaction conditions. DFT calculations reveal that the defect‐rich surface of the plasma‐oxidized silver foils in the presence of local electric fields drastically decrease the overpotential of CO2 electroreduction.

Enhanced Carbon Dioxide Electroreduction to Carbon Monoxide over Defect-Rich Plasma-Activated Silver Catalysts.

Efficient, stable catalysts with high selectivity for a single product are essential if electroreduction of CO2 is to become a viable route to the synthesis of industrial feedstocks and fuels. A plasma oxidation pre-treatment of silver foil enhances the number of low-coordinated catalytically active sites, which dramatically lowers the overpotential and increases the activity of CO2 electroreduction to CO. At -0.6 V versus RHE more than 90 % Faradaic efficiency towards CO was achieved on a pre-oxidized silver foil. While transmission electron microscopy (TEM) and operando X-ray absorption spectroscopy showed that oxygen species can survive in the bulk of the catalyst during the reaction, quasi in situ X-ray photoelectron spectroscopy showed that the surface is metallic under reaction conditions. DFT calculations reveal that the defect-rich surface of the plasma-oxidized silver foils in the presence of local electric fields drastically decrease the overpotential of CO2 electroreduction.

Oxygen Sensing in the Pulmonary Circulation

Since the original description of hypoxic pulmonary vasoconstriction (HPV) by Von Euler and Liljestrand in 1946, where they concluded, “breathing of pure oxygen lowered the pulmonary arterial pressure and oxygen-lack raised it,”1 the precise oxygen-sensing mechanism within the lungs has remained an enigma. Nevertheless, there seems to be some agreement to an overall mechanism for HPV: the primary oxygen sensor is the pulmonary artery smooth muscle cells (PASMC) mitochondrial electron transport chain (ETC); the ETC-produced superoxide/reactive oxygen species (ROS) is the mediator; and redox-sensitive plasma membrane voltage-gated potassium (Kv) channels are the effectors.2 Intriguingly, a similar sensor-mediator-effector model seems to operate in other areas where oxygen is sensed in the body, such as the ductus arteriosus or the carotid body.2 But many controversies exist. Although several groups, including ours, show that acute hypoxia decreases superoxide production from ETC complexes I and III, others find that hypoxia increases superoxide production.2,3 Regardless, most agree that it is the more stable and diffusible hydrogen peroxide (H2O2), produced from superoxide via the mitochondrial MnSOD (manganese superoxide dismutase) that eventually reaches the cell membrane to regulate Kv channels.2,3 However, once again controversy exists. Many groups, including ours, show that decreased levels of H2O2 (a reducing signal) directly inhibits Kv channels (like Kv1.5),2,3 depolarizing the plasma membrane, increasing Ca2+ influx through L-type Ca2+ channels, and causing PASMC contraction2,3 (Kv channels are intrinsically redox sensitive and animals lacking Kv1.5 lack HPV4). Others suggest that increased levels of H2O2 (an oxidative signal) primarily result in an endoplasmic reticulum-mediated calcium release, with K+ channel inhibition as a downstream effect.3 Much has been written about the first controversy, which tends to …

Identification of oxidative modifications of hemopexin and their predicted physiological relevance

Hemopexin protects against heme toxicity in hemolytic diseases and conditions, sepsis, and sickle cell disease. This protection is sustained by heme-hemopexin complexes in biological fluids that resist oxidative damage during heme-driven inflammation. However, apo-hemopexin is vulnerable to inactivation by reactive nitrogen (RNS) and oxygen species (ROS) that covalently modify amino acids. The resultant nitration of amino acids is considered a specific effect reflecting biological events. Using LC-MS, we discovered low endogenous levels of tyrosine nitration in the peptide YYCFQGNQFLR in the heme-binding site of human hemopexin, which was similarly nitrated in rabbit and rat hemopexins. Immunoblotting and selective reaction monitoring were used to quantify tyrosine nitration of in vivo samples and when hemopexin was incubated in vitro with nitrating nitrite/myeloperoxidase/glucose oxidase. Significantly, heme binding by hemopexin declined as tyrosine nitration proceeded in vitro Three nitrated tyrosines reside in the heme-binding site of hemopexin, and we found that one, Tyr-199, interacts directly with the heme ring D propionate. Investigating the oxidative modifications of amino acids after incubation with tert-butyl hydroperoxide and hypochlorous acid in vitro, we identified additional covalent oxidative modifications on four tyrosine residues and one tryptophan residue of hemopexin. Importantly, three of the four modified tyrosines, some of which have more than one modification, cluster in the heme-binding site, supporting a hierarchy of vulnerable amino acids. We propose that during inflammation, apo-hemopexin is nitrated and oxidated in niches of the body containing activated RNS- and ROS-generating immune and endothelial cells, potentially impairing hemopexin's protective extracellular antioxidant function.

Facile synthesis of La2O2CO3 nanoparticle films and Its CO2 sensing properties and mechanisms

In this paper, we presented a simple method to fabricate size-controlled La2O2CO3 nanoparticle by annealing La(OH)3 nanocrystallines in air atmosphere. The microstructures of the samples were analyzed by high resolution transmission electron microscope (HRTEM), X-ray diffraction (XRD) and scanning electron microscope (SEM). TEM images indicate that the La(OH)3 precursors consists of uniform ellipsoids with width of 9–15nm and length of 15–30nm and La2O2CO3 are spheroidal particles with size of 12–25nm. XRD patterns indicate that La(OH)3 nanocrystallines are hexagonal phase and transform to monoclinic La2O2CO3 after annealing. And then, La2O2CO3 nanoparticle is printed on an interdigital electrode as a sensing material for CO2 detection. La2O2CO3 sensor exhibits good cycle stability performance and fast response and recovery (53s and 120s) over the wide range of 300–5000ppm CO2 in air condition. In addition, we also investigate the effect of oxygen concentration in the background atmosphere on CO2 response of La2O2CO3 sensor. The CO2 sensing mechanisms for La2O2CO3 sensor can be attributed to the interaction of CO2 with oxygen species on La2O2CO3 surface including chemisorption, surface reaction and desorption process, which also can be used to explain other metal oxide based CO2 gas sensor.

A colorimetric and near-infrared fluorescent probe for hydrogen polysulfides and its application in living cells

The development of probes for rapid, selective, and sensitive detection of the hydrogen polysulfides is of great importance in biological science. We report here a new Near-infrared (NIR) fluorescent off-on probe for selective and sensitive detection of hydrogen polysulfides (H2Sn) with colorimetric and NIR fluorescent dual signal changes. The probe was synthesized by an esterification reaction coupling between a dicyanomethylene-benzopyran (DCMB) dye and a bis-electrophilic H2Sn capture group 2-fluoro-5-nitrobenzoic acid. The probe showed a specific off-on response to H2Sn in aqueous solution with nanomolar LOD, and without interference by a range of competing sulfocompounds and several reactive nitrogen and oxygen species. Moreover, it can be used for imaging of endogenous H2Sn in living cells.

Deconvolution of the Response to Bacillus Calmette-Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity.

Bacillus Calmette–Guérin (BCG) is used as a vaccine and diagnostic test for tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While clinically useful, the response to mycobacterial stimulation is complex and the induced protein signature remains poorly defined. We characterized the cell types directly engaged by BCG, as well as the induced cytokine loops that transmit signal(s) to bystander cells. Standardized whole-blood stimulations and mechanistic studies on single and purified cell populations identified distinct patterns of activation in monocytes as compared to neutrophils and invariant lymphocyte populations. Deconvoluting the role of Toll-like receptor 2/4 and Dectin-1/2 in the inflammatory response to BCG, we revealed Dectin-1/2 as dominant in neutrophils as compared to monocytes, which equally engaged both pathways. Furthermore, we quantified the role of NF-κB and NADPH/reactive oxygen species (ROS)-dependent cytokines, which triggered a JAK1/2-dependent amplification loop and accounted for 40–50% of the induced response to BCG. In sum, this study provides new insight into the molecular and cellular pathways involved in the response to BCG, establishing the basis for a new generation of immunodiagnostic tools.

Oxygen redox reactions in Li ion battery electrodes studied by resonant inelastic X-ray scattering

We present results using inelastic scattering X-ray spectroscopy (RIXS) combined with X-ray absorption spectroscopy on Li ion battery cathode and anode materials, respectively. In particular, we discuss results obtained on the cathode materials Li1.2[Ni0.13Co0.133Mn0.544]O2 and Lix[Ni0.65Co0.25Mn0.1]O2 as well as in the composite anode material Ni0.5TiOPO4/C. We show that oxygen redox reactions are an important aspect of many such systems and how one can successfully address them using RIXS. New insights on the formation of new oxygen species and on the details of cycling-induced structural disorder can be detected. We foresee a particular future focus on these issues considering the rapid development of new operando RIXS techniques for Li ion battery research.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome.

Background:Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS.Methods:The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t-test, Mann-Whitney U-test, and Chi-square test were used to analyze the results.Results:The fasting blood glucose (z = 3.52, P = 0.001), hs-CRP (z = 3.23, P = 0.004), ox-LDL (z = 2.62, P = 0.013), and e-NOS (z = 2.22, P = 0.026) levels and cardiac risk score (z = 5.23, P < 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P = 0.002) in MetS patients but not in the control group.Conclusions:Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients with MetS, smoking is independently related to endothelial dysfunction.

Neuroglobin, an oxygen-binding protein in the mammalian nervous system (localization and putative functions)

The review summarizes current data on neuroglobin, the heme-containing protein discovered in mammalian nerve cells in 2000. It presents general characteristics of neuroglobin as well as data on its evolutionary changes and expression across different taxa. Neuroglobin distribution in specific brain structures and outside the brain is described. The issue of the occurrence of neuroglobin not only in neurons but also in astroglial cells is discussed. Subcellular localization of neuroglobin is characterized with a special focus on its detection in the nucleus of nerve cells, suggesting its involvement in nuclear functions. Current ideas on the probable functional significance of neuroglobin are reported. Neuroglobin is presumed to be involved in metabolism of reactive nitrogen and oxygen species as well as in intracellular signaling pathways. Besides, neuroglobin has neuroprotective and antiapoptotic functions. Since its expression changes during ontogenesis, its neuroprotective role in ageing is specifically highlighted. Changes in expression and localization of neuroglobin are suggested to influence the adaptive potential of an organism.

Insight into carbon deposition associated with NiCo/MgO catalyzed CH4/CO2 reforming by using density functional theory

A density-functional theory method has been conducted to investigate carbon deposition associated with NiCo/MgO catalyzed CH4/CO2 reforming. In the process of carbon deposition formation, CH4 dissociation to produce C, further C accumulates to form carbon deposition. In addition, C and its precursor can be eliminated by oxygen species from CO2 dissociation. Based on above analysis about carbon deposition, three possible ways are considered to contribute to resist carbon deposition (1) reducing CH4 dissociation to decrease C produced; if not, (2) accelerating CHx(x=0∼3) oxidation to eliminate C, (3) blocking C accumulation, further suppressing carbon deposition, that is, the rate of CHx oxidation is more than that of C accumulation. The calculation results show that the dissociation of CH4 has almost equal activation energy on perfect and defective NiCo/MgO, and they are lower than those on Ni/MgO and NiCo(111), indicating that it is impossible to reduce C produce through reducing CH4 dissociation when addition a second metal Co to Ni/MgO or using different support MgO; CH oxidation is favorable to produce CHO compared to CH dissociation into C and H, further it is favorable for CHO dissociation into CO and H on perfect and defective NiCo/MgO catalyst. In addition, C oxidation is easier on defective NiCo/MgO than that on perfect NiCo/MgO, meanwhile it is easier on NiCo/MgO than that on NiCo(111), indicating that using defective MgO support accelerates C oxidation, further elimination carbon deposition. Carbon accumulation is easier on perfect NiCo/MgO than that on defective NiCo/MgO. The results indicate that the defective MgO surface support NiCo bimetal catalyst is more resistant to carbon deposition than perfect one. One can modify the Ni-based catalyst behavior via addition a second metal Co or using MgO support with oxygen-vacancy. This might be given a clue for experimental catalyst to develop Ni-based catalyst with the property of resisting carbon deposition.

Abstract 2327: Apoptosis of melanoma induced by non-thermal atmospheric pressure bio-compatible plasma activated media

Abstract Melanoma is the most dangerous type of skin cancer, which mostly related with the exposure of ultraviolet (UV), and especially happened to those who have low skin pigment levels. Epidemiological studies showed Europeans and North Americans have a high incidence of melanoma, while it is less common in Asia and Africa. Therefore, the new and more effective methods to treat melanoma are still necessarily needed. Non-thermal atmospheric pressure bio-compatible plasma (NBP) is defined as a partially ionized gas with electrically charged particle, which has been reported have cytotoxicity on various cancer cells induce DNA damage and apoptosis other than normal cells. Reactive oxygen and/or nitrogen species (RONS) were proved to play the most important role during this process, by inducing oxidative stress and depolarization of mitochondria membrane potential with the consequence of various cancer cells apoptosis. The plasma activated media (PAM), which the media treated directly by NBP with different time, containing mostly long-live secondary species such as hydrogen peroxide (H2O2) which have been confirmed anti-microorganism and cytotoxic activity. Researches already investigated that PAM also effective in cancer therapy via inducing apoptosis. However, the underlying molecular mechanisms of apoptosis are remaining elusive. The purpose of this study was to evaluate the potential of PAM as an effective tool to induce apoptosis in melanoma cells. Our results showed that PAM has a killing effect to melanoma cells in a time-dependent manner, for 3minutes treatment could induce almost 40% cells entry death, after treated by 5 minutes more than 60%, and 10 minutes treatment reduced the cell viability to approximately 30%. Annexin-V/PI staining demonstrated that PAM kills these cells via apoptosis pathway. We also found that with a manner of treatment time PAM significantly increased the concentration of intracellular NO and H2O2, reflecting an influx of extracellular RONS may result in melanoma cells apoptosis. Besides, western blot assay showed that P53 and caspase 3 increased after PAM treatment. Taken together, PAM is effective to induce the apoptosis in melanoma cells in vitro, further in vivo experiments will be performed to investigate the functional effects in the animals. Citation Format: Ihn Han, Ying Li, Eun Ha Choi. Apoptosis of melanoma induced by non-thermal atmospheric pressure bio-compatible plasma activated media [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2327. doi:10.1158/1538-7445.AM2017-2327

Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10μg/ml) significantly attenuated the decrease in cell viability in H2О2-induced oxidative stress (0.1mM H2О2), thus showing an effective in vitro protection.In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol − induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18mg/kg b.w., 7days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury.

Comparative responses of chicken macrophages to infection with Salmonella enterica serovars

Poultry products such as meat and eggs are known reservoirs for Salmonella serovars. Macrophages play an important role by limiting bacterial replication using several defense mechanisms including immune and inflammatory mediators, antibacterial proteins, reactive nitrogen and oxygen species. In this study, we evaluate transcriptional changes in Toll-like receptors, immune/inflammatory cytokines, chemokines, antibacterial factors, and nitric oxide (NO) production in HD11 chicken macrophages in response to intracellular persistence of poultry-derived Salmonella enterica Enteritidis (SE), Typhimurium (ST), and Heidelberg (SH) that were associated with human salmonellosis. Invasion of ST was higher than SE or SH; however, SH persistence in HD11 cells at 18 h post infection (hpi) was more pronounced than the other 2 serovars. In comparison to the uninfected control HD11 cells, expression of TLR5 was >2 fold higher for SE and SH which was followed by up-regulation of downstream signal transduction molecules. Significant up-regulation of antibacterial peptides, proinflammatory chemokines, cytokines, and NO production were observed in response to SE, SH, and ST at 18 hpi. These results indicate that although antibacterial factors contribute to the clearance of invading Salmonella, some of the differences in response could also be due to the different virulence properties of these serovars.

Three-dimensional ordered ZnO–Fe3O4 inverse opal gas sensor toward trace concentration acetone detection

Three-dimensional inverse opal (3DIO) ZnO-Fe3O4 composite structure was prepared by a template method and the gas sensing property was investigated toward trace acetone which is an important biomarker of diabetes. The prepared 3DIO composite sensors have large surface area due to both macropores (larger than 100nm) and mesoporous structure in skeleton, which make the inner surface accessible and provide more active sites to adsorb more oxygen species and target molecules. 3DIO ZnO-Fe3O4 composite sensor exhibits much higher response toward acetone relative to pure ZnO sensor. The optimal 3DIO sensor exhibited a detection limit as low as 100ppb acetone and showed 40% response increase from 0.9ppm (healthy humans) to 1.8ppm (diabetics) which allow reliable diagnosis of diabetic patients by acetone monitoring.

Transforming growth factor β1 (TGFβ1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of fatal outcome. The lack of information about the signaling pathways that sustain fibrosis and the myofibroblast phenotype has prevented the development of targeted therapies for IPF. Our previous study showed that isolated fibrogenic lung fibroblasts have high endogenous levels of the hyaluronan receptor, CD44V6 (CD44 variant containing exon 6), which enhances the TGFβ1 autocrine signaling and induces fibroblasts to transdifferentiate into myofibroblasts. NADPH oxidase 4 (NOX4) enzyme, which catalyzes the reduction of O2 to hydrogen peroxide (H2O2), has been implicated in the cardiac and lung myofibroblast phenotype. However, whether CD44V6 regulates NOX4 to mediate tissue repair and fibrogenesis is not well-defined. The present study assessed the mechanism of how TGF-β-1-induced CD44V6 regulates the NOX4/reactive oxygen species (ROS) signaling that mediates the myofibroblast differentiation. Specifically, we found that NOX4/ROS regulates hyaluronan synthesis and the transcription of CD44V6 via an effect upon AP-1 activity. Further, CD44V6 is part of a positive-feedback loop with TGFβ1/TGFβRI signaling that acts to increase NOX4/ROS production, which is required for myofibroblast differentiation, myofibroblast differentiation, myofibroblast extracellular matrix production, myofibroblast invasion, and myofibroblast contractility. Both NOX4 and CD44v6 are up-regulated in the lungs of mice subjected to experimental lung injury and in cases of human IPF. Genetic (CD44v6 shRNA) or a small molecule inhibitor (CD44v6 peptide) targeting of CD44v6 abrogates fibrogenesis in murine models of lung injury. These studies support a function for CD44V6 in lung fibrosis and offer proof of concept for therapeutic targeting of CD44V6 in lung fibrosis disorders.

Research on Sensitization Effect of Ceria Nanoparticles on Tin Oxide Wire-in-Tube Nanofibers

To elaborate the effect of CeO2 nanoparticles on the sensing properties of SnO2, CeO2-functionalized SnO2 wire-in-tube nanofibers (WITN) was prepared by electrospinning and subsequently impregnating treatment. The gas sensing studies revealed that the CeO2 loaded SnO2 WITN exhibited enhanced sensitivity to ethanol compared to the pristine SnO2. With increasing amount of CeO2, the response of nanocomposites increases firstly and then decreases. And the response of nanocomposites to ethanol reach maximum when the concentration of impregnated Ce (NO3)3·6H2O is 0.03 mol·L-1. To detail the sensing mechanism, the X-ray photoelectron spectroscopy was firstly employed to detect the variation in oxygen species corresponding to different amounts of CeO2, but no obviously changes in oxygen species was detected. Subsequently, it was found that the initial resistance of CeO2@SnO2 WITN was higher than pristine SnO2, which could be beneficial to the improvement of sensing properties. More importantly, oxygen vacancy (mainly offered by CeO2 nanoparticles) was proved to be positively correlated to their gas-sensing performance. In this work, the electronic sensitization mechanism based on CeO2 loaded SnO2 was detailed, which could help for the better understanding the sensitization effect of rare earth element on semiconductor oxides.